Expression of 8-oxoguanine Glycosylase in Human Fetal Membranes

Authors

  • Ramkumar Menon,

    Corresponding author
    1. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine and Perinatal Research, The University of Texas Medical Branch at Galveston, Galveston, TX, USA
    • Correspondence

      Ramkumar Menon, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine Perinatal Research, The University of Texas Medical Branch at Galveston, 301 University Boulevard; MRB, Room 11.138, Galveston, TX 77555-1062, USA.

      E-mail: ra2menon@utmb.edu

    Search for more papers by this author
  • Jossimara Polettini,

    1. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine and Perinatal Research, The University of Texas Medical Branch at Galveston, Galveston, TX, USA
    2. Department of Pathology, Botucatu Medical School, UNESP – Univ. Estadual Paulista, Botucatu, Sao Paulo, Brazil
    Search for more papers by this author
  • Tariq Ali Syed,

    1. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine and Perinatal Research, The University of Texas Medical Branch at Galveston, Galveston, TX, USA
    Search for more papers by this author
  • George R. Saade,

    1. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine and Perinatal Research, The University of Texas Medical Branch at Galveston, Galveston, TX, USA
    Search for more papers by this author
  • Istvan Boldogh

    1. Department of Microbiology and Immunology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA
    Search for more papers by this author

Abstract

Problem

The most common DNA lesion generated by oxidative stress (OS) is 7, 8-dihydro-8-oxoguanine (8-oxoG) whose excision repair is performed by 8-oxoguanine glycosylase (OGG1). We investigated OGG1 expression changes in fetal membranes from spontaneous preterm birth (PTB) and preterm premature rupture of the membranes (pPROM) and its changes in vitro in normal fetal membranes exposed to OS inducer water-soluble cigarette smoke extract (CSE).

Method of study

DNA damage was determined in amnion cells treated with CSE by comet and FLARE assays. OGG1 mRNA expression and localization in fetal membranes from clinical specimens and in normal term membranes exposed to CSE were examined by QRT-PCR and by immunohistochemistry.

Results

DNA strand and base damage was seen in amnion cells exposed to CSE. OGG1 expression was 2.5-fold higher in PTB samples compared with pPROM (P = 0.045). No significant difference was seen between term and pPROM or PTB and term. CSE treatment showed a nonsignificant decrease in OGG1. OGG1 was localized to both amnion and chorion with less intense staining in pPROM and CSE-treated membranes.

Conclusion

Increased OS-induced DNA damage predominated by 8-oxoG is likely to persist in fetal cells due to reduced availability of base excision repair enzyme OGG1. This can likely lead to fetal cell senescence associated with some adverse pregnancy outcome.

Ancillary